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“A new morning-after pill can be used up to five days after sex, longer than any protection against pregnancy developed so far”, the Daily Mail reported. It said a trial of the new drug found it prevents up to two-thirds of unwanted pregnancies if taken within 72 hours, and 50% if taken within five days.

This trial compared the effectiveness of two emergency contraceptives, EllaOne (ulipristal acetate) and Levonelle (levonorgestral). Levonelle is the main oral emergency contraceptive in the UK and is available from pharmacists without a prescription. It is approved for use up to 72 hours (three days) after unprotected sex. EllaOne is approved for use up to 120 hours (five days), but is a prescription only medicine available through GPs.

The drugs appeared to be equally effective at preventing pregnancy if taken within 72 hours of having sex. The researchers also combined data from an earlier study to look at the effectiveness of this medication after 72 hours. Their research confirms the licensed indication for this drug, but because few women became pregnant in the studies, larger post-marketing studies will be needed to assess just how effective the new drug is at preventing pregnancy after 72 hours.

Protected sex is obviously the best option, but if emergency contraception is needed, the sooner it is taken the better. EllaOne is at least as good as Levonelle in the first 72 hours after unprotected sex, but may also be used up to 120 hours (five days) after unprotected sex. The copper intrauterine device can also be used for up to five days.

 

Where did the story come from?

This research was carried out by Professor Anna F. Glasier from Edinburgh University and other researchers from US universities. The research was carried out for HRA pharma, which makes a ulipristal acetate product called ellaOne. The study was published in the (peer-reviewed) medical journal: The Lancet.

The newspapers focussed on the potential social impact of an emergency contraceptive pill that can be taken five days after unprotected sex. Neither the Daily Mail’s suggestion the pill is still 50% effective five days after sex, or the Sun’s statement that it prevents 98% of pregnancies five days after sex are supported by the research.

 

What kind of research was this?

This is a randomised non-inferiority trial, a type of randomised controlled trial that assesses whether a new drug is at least as good as an existing treatment. This study tested whether ulipristal acetate, a contraceptive pill, was as effective as levonorgestrel as emergency contraception when taken within 72 hours of unprotected sex. Levonorgestral is the main oral emergency contraceptive licensed in the UK, but is not effective when taken more than 72 hours after unprotected sex.

The researchers also carried out a meta-analysis comparing the effectiveness of ulipristal acetate with levonorgestrel, using this data and data from a previous study.

 

What did the research involve?

In the non-inferiority trial, the researchers recruited 2,221 women from 35 family planning centres in the UK, Ireland and the US. The women had to be older than 16 (UK) or 18 (USA) with regular menstrual cycles and seeking emergency contraception up to five days after having had unprotected sex. The study excluded women who were pregnant, breastfeeding, sterilised, taking the contraceptive pill or were fitted with an intrauterine contraceptive device, or whose partner had been sterilised.

Where suitable, women who presented to the clinic 72 or more hours after sex were initially offered an intrauterine device which can be used as emergency contraception within five days after sex.

All women had a pregnancy test and a blood sample taken when they arrived at the clinic. They were then grouped into those who had sex less than 72 hours beforehand and those who had sex between 72 and 120 hours before. Within these two groups, the women were randomly assigned to receive either ulipristal acetate or levonorgestral.

After receiving either pill, the women were asked to keep a diary of their sexual activity, use of contraception, vaginal bleeding, whether they were on any other medication or any side effects they experienced.

The women were followed up until five to seven days after their next expected period. If their period was delayed they were followed and given routine pregnancy tests.

The study was designed to examine differences in pregnancy rates in women who took the two treatments within 72 hours of unprotected sex, and this was the primary outcome of the study. A secondary outcome was pregnancy rates in the much smaller number of women who took the emergency contraceptives after the recommended time of 72 hours.

 

What were the basic results?

There were 1,696 women who received emergency contraception within 72 hours of having had sex. There were 15 pregnancies out of the 844 women in the ulpristal acetate group and 22 out of 852 in the levonorgestral group. There was no difference between the two types of pill at preventing pregnancy when given within 72 hours (odds ratio 0.68, 95% confidence interval 0.35 to 1.31).

There were 203 women who used emergency contraceptive pills between 72 and 120 hours. Three women out of 106 in the levonorgestral group became pregnant. There were no pregnancies in the 97 women who received ulipristal acetate.

Similar numbers of women reported side effects with both drugs, in both causes 94% of these side effects were mild or moderate.

The researchers also compared and combined this data with a data from a 2006 randomised controlled trial that had compared ulipristal acetate to levonorgestral in 1,546 women. There were some differences between the studies, including the women in the non-inferiority trial being on average younger, with a higher body mass index and more likely to have waited longer before taking emergency contraception (39.7 hours vs 35.3 hours). These differences were adjusted for in the analyses.

When the two trials were combined, there were more pregnancies in the levonorgestral group than the ulipristal acetate group when the data was analysed in groups that took the pill within 24 hours, within 72 hours and within 120 hours. The difference was of borderline significance for the within 72 hour group. Odds ratios for the within 24 hours group was 0.35 OR, 95% CI 0.11 to 0.93, for the within 72 hours group: 0.58 OR, 95% CI 0.33 to 0.99,and for the within 120 hours group: 0.55 OR, 0.32 to 0.93).

 

How did the researchers interpret the results?

The researchers concluded, “ulipristal acetate provides women and health-care providers with an alternative choice for emergency contraception that can be used up to five days after unprotected sexual intercourse”.

They suggest that neither study alone had enough participants to assess a statistical difference between levonorgestral and ulipristal acetate. However, combining the two indicated that ulipristal acetate prevented more pregnancies than levonorgestral when taken within 24 hours or 120 hours after unprotected sexual intercourse.

They also commented that levonorgestral prevented less pregnancies in their study than they were expecting based on the World Health Organisation’s (WHO) estimations of effectiveness when taken at increasing lengths of time after unprotected sex.

 

Conclusion

This study shows that ulipristal acetate is as least as effective as levonorgestral as an emergency contraception pill when taken within 72 hours of unprotected intercourse. The researchers combined their data with data from a previous study to test whether ulipristal acetate was more effective than levonorgestral when taken up to 120 hours after unprotected sex and found there were fewer pregnancies in the ulipristal acetate group.

The study has some limitations, some of which the researchers highlight:

• This study was conducted at family planning centres. However, emergency contraception is available at pharmacists without prescription. The study also excluded women taking the contraceptive pill and emergency contraception is frequently used by women who have missed taking a pill. As such, the women in this study may not be totally representative of these other populations.
• The WHO states that the effectiveness of levonorgestral decreases with time. As such, it recommends that women take the pill at the earliest opportunity. The researchers in this study did not examine how fast the effectiveness of ulipristal acetate reduces.
• The drugs’ effectiveness at preventing pregnancy when taken more than 72 hours after sex was only a secondary outcome of this study. Also, as it involved only three unwanted pregnancies, it will be important to test how well the drug works after 72 hours in trials designed to look at its use up to 120 hours.
• Although the researchers combined data with an earlier study to look at the effectiveness of the emergency contraceptives on a larger population, further primary research would be needed to confirm these findings.

Levonorgestral is currently the main oral medication licensed in the UK for use as an emergency contraceptive. Women should be assured that it is highly effective if taken correctly, and within 72 hours (three days) of unprotected intercourse. The earlier the pill is taken, the more effective it is, with the optimal time to taking the pill being within 12 hours.

Ulipristal acetate has recently been licensed for use in the UK, and will be marketed for women within five days of unprotected intercourse. The alternative at the moment is a copper intrauterine device which can be used up to five days after unprotected intercourse. More research of ulipristal acetate compared to these devices can be expected.

Links To The Headlines

New morning after pill ‘can be taken up to five days after sex’. The Daily Telegraph, January 29 2010

5-day pill to ‘dump’ a baby. The Sun, January 29 2010

Five-day limit for post-sex pill. BBC News, January 29 2010

Morning-after pill that works five days later. Daily Mail, January 29 2010

New-morning after drug is abortion pill, campaigners say. The Times, January 29 2010

Pill that can halve birth risk. Daily Express, January 29 2010

Links To Science

Glasier AF,  Cameron ST,  Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. The Lancet, Early Online Publication, 29 January 2010

“The noise caused by wind farms can make some people ill”, reported The Daily Telegraph. It said experts have dismissed the idea of a "wind turbine syndrome" as a special cause of headaches, nausea and panic attacks, but have acknowledged that the irritation caused by the noise can affect certain individuals.

The story is based on an industry commissioned review of the current research on the possible health effects of wind turbine noise. It found that the sound (including subaudible sound) is not unique, and does not pose a risk to human health. Although the sound may cause ‘annoyance’ for some people, this in itself is not an adverse health effect.

This research is unlikely to resolve the controversy over the potential health effects from wind turbines. This is mainly because the research on which the review was based is not sufficient to prove or disprove that there are health effects. The review itself also had some methodological shortcomings, and the reviewing group did not include an epidemiologist, usually a given for assessing  potential environmental health hazards.

Further research on this issue is needed. Ideally this would involve comparing people exposed to wind turbine noise with well-matched control subjects who have not had that exposure. These studies should also carefully evaluate the psychological harms of noise exposure.

 

Where did the story come from?

The news report is centred around a review by a panel of independent experts looking into the issue of Wind Turbine Syndrome. Their review, called “Wind Turbine Sound and Health Effects”, was presented at a meeting of the Institute of Acoustics Wind Turbine Noise in Cardiff on Wednesday January 27. The presentation was made by one of the experts on the panel, Dr Geoff Leventhall, a UK-based noise and vibration consultant.

Dr Leventhall carried out the review with Dr David Colby, an associate professor at the University of Western Ontario, and other independent experts in medicine, public health, audiology and acoustics. The panel aimed to “provide an authoritative reference document for legislators, regulators, and anyone who wants to make sense of the conflicting information about wind turbine sound”. The review was commissioned by the American Wind Energy Association and the Canadian Wind Energy Association.

 

What kind of research was this?

This was a non-systematic literature review of the available literature on the perceived health effects of wind turbines.

 

What did the research involve?

The panel of experts began their literature review by searching the scientific database PubMed for studies under the heading “Wind Turbines and Health Effects” and “vibroacoustic disease”. They provide an extensive reference list of peer-reviewed and non-peer-reviewed sources.

The researchers reviewed the studies that looked at infrasound (a low frequency sound wave that cannot usually be heard) sounds that can be heard, and the vibration produced by wind turbines. The researchers were looking for answers to the following questions:

• How do wind turbine operations affect human hearing?
• How do wind turbines produce sound, and how is it measured and tested?
• What type of exposure to wind turbines is more likely to be perceived by humans (low-frequency sound, infrasound or vibration)?
• What are the potential adverse effects and health implications of sound exposure?

The researchers say that infrasound is defined as acoustic oscillations with frequencies below audible sound levels (about 16 Hz). Low-frequency sound, they say, is typically considered as sound that can be heard in the 10 Hz to 200 Hz range, but it is not closely defined.

They also considered how to define ‘annoyance’, which is a subjective response to many types of sounds, which varies among people. They acknowledge that constant low frequency sounds can be a frustrating experience for people, but say it is not considered an adverse health effect or disease. They say that annoyance from airports, road traffic, etc. cannot be predicted easily with a sound level meter.

The researchers give an overview of the evidence on the effects of noise exposure in general. They also give detailed descriptions of the research they found on the effects of wind turbine noise. They say these case series, though important for raising suspicion of harm, cannot show causation. For this, repeated case-control studies or cohort studies are needed.

 

What were the basic results?

The researchers describe the effect of various sounds on ‘annoyance’. They say that as sound gets louder, more people who hear it will become distressed until nearly everybody is affected. But this will occur to varying degrees. They say it is not clear why some people continue to be adversely affected by sound when it reverts to a low level. This occurs at all frequencies, although there seems to be more subjective variability at the lower frequencies.

The ‘nocebo’ effect is discussed, which is the opposite of the ‘placebo’ effect. This is where an adverse outcome, a worsening of mental or physical health is based on fear or belief in adverse effects.

The researchers also describe the studies they identified that looked at ‘wind turbine syndrome’, where symptoms are said to include sleep disturbance, headache, ringing in the ears, ear pressure, dizziness, nausea, visual blurring, fast heart beats, irritability, poor concentration, memory, panic attacks, internal pulsation, and quivering. They say that the syndrome has no physiological or pathological mechanism behind it, but is an example of the well-known stress effects of exposure to noise, as displayed by a small proportion of the population.

 

How did the researchers interpret the results?

The panel reached agreement on three key points:

• There is no evidence that the sounds emitted by wind turbines have any direct adverse physiological effects.
• The ground-borne vibrations from wind turbines are too weak to be detected by, or to affect, humans.
• The sounds emitted by wind turbines are not unique. There is no reason to believe, based on the levels and frequencies of the sounds and the panel’s experience with sound exposures in occupational settings, that the sounds from wind turbines could plausibly have direct adverse health consequences.

They conclude that the collective symptoms in some people exposed to wind turbines are more likely to be associated with annoyance at the low sound levels from wind turbines, rather than directly caused by them.

 

Conclusion

This is a non-systematic review of literature. There are several points to be made about this research:

• There is no clear description of the methods the researchers used to search for available research, nor how they rated the quality of the research they found. Therefore, it is not possible to say that all relevant research was identified, or comment on the reliability of the research that was included.
• This review panel was commissioned by an industry group, and included a variety of academic perspectives, but not an epidemiologist. Someone with this specific skill set should be included when environmental health hazards are assessed.
• The link between psychological distress and physical symptoms has not been explored by this report. The acknowledgment that some people exposed to wind turbine noise suffer annoyance suggests that monitoring and maximum permitted levels need to be considered carefully in areas where turbines are planned.

Overall, this review will probably not resolve this controversy as there was a lack of high-level evidence on which to base any solid conclusions. What is now needed are studies that compare people exposed to turbine noise with well-matched control subjects who have not had that exposure. These studies should also carefully evaluate the psychological harms of noise exposure.

Links To The Headlines

Wind farms can cause noise problems finds study. The Daily Telegraph, January 28 2010

Conference over claims wind farms are health risk. BBC News, January 28 2010
 

Links To Science

Colby WD, Dobie R, Leventhall G, et al. Wind Turbine Sound and Health Effects. An Expert Panel Review. December 2009